Predicting effects on oxaliplatin clearance: in vitro, kinetic and clinical studies of calcium- and magnesium-mediated oxaliplatin degradation

Abstract This study evaluated the impact of calcium and magnesium on the in vitro degradation and in vivo clearance of oxaliplatin. Intact oxaliplatin and Pt(DACH)Cl2 were measured in incubation solutions by HPLC-UV. A clinical study determined changes in plasma concentrations of calcium and magnesi...

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Autores principales:	Catherine H. Han, Prashannata Khwaounjoo, Andrew G. Hill, Gordon M. Miskelly, Mark J. McKeage
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4d56bc64c892498384d45ce82fe2a83d
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spelling	oai:doaj.org-article:4d56bc64c892498384d45ce82fe2a83d2021-12-02T16:06:33ZPredicting effects on oxaliplatin clearance: in vitro, kinetic and clinical studies of calcium- and magnesium-mediated oxaliplatin degradation10.1038/s41598-017-04383-42045-2322https://doaj.org/article/4d56bc64c892498384d45ce82fe2a83d2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04383-4https://doaj.org/toc/2045-2322Abstract This study evaluated the impact of calcium and magnesium on the in vitro degradation and in vivo clearance of oxaliplatin. Intact oxaliplatin and Pt(DACH)Cl2 were measured in incubation solutions by HPLC-UV. A clinical study determined changes in plasma concentrations of calcium and magnesium in cancer patients and their impact on oxaliplatin clearance. Kinetic analyses modelled oxaliplatin degradation reactions in vitro and contributions to oxaliplatin clearance in vivo. Calcium and magnesium accelerated oxaliplatin degradation to Pt(DACH)Cl2 in chloride-containing solutions in vitro. Kinetic models based on calcium and magnesium binding to a monochloro-monooxalato ring-opened anionic oxaliplatin intermediate fitted the in vitro degradation time-course data. In cancer patients, calcium and magnesium plasma concentrations varied and were increased by giving calcium gluconate and magnesium sulfate infusions, but did not alter or correlate with oxaliplatin clearance. The intrinsic in vitro clearance of oxaliplatin attributed to chloride-, calcium- and magnesium-mediated degradation predicted contributions of <2.5% to the total in vivo clearance of oxaliplatin. In conclusion, calcium and magnesium accelerate the in vitro degradation of oxaliplatin by binding to a monochloro-monooxalato ring-opened anionic intermediate. Kinetic analysis of in vitro oxaliplatin stability data can be used for in vitro prediction of potential effects on oxaliplatin clearance in vivo.Catherine H. HanPrashannata KhwaounjooAndrew G. HillGordon M. MiskellyMark J. McKeageNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Catherine H. Han Prashannata Khwaounjoo Andrew G. Hill Gordon M. Miskelly Mark J. McKeage Predicting effects on oxaliplatin clearance: in vitro, kinetic and clinical studies of calcium- and magnesium-mediated oxaliplatin degradation
description	Abstract This study evaluated the impact of calcium and magnesium on the in vitro degradation and in vivo clearance of oxaliplatin. Intact oxaliplatin and Pt(DACH)Cl2 were measured in incubation solutions by HPLC-UV. A clinical study determined changes in plasma concentrations of calcium and magnesium in cancer patients and their impact on oxaliplatin clearance. Kinetic analyses modelled oxaliplatin degradation reactions in vitro and contributions to oxaliplatin clearance in vivo. Calcium and magnesium accelerated oxaliplatin degradation to Pt(DACH)Cl2 in chloride-containing solutions in vitro. Kinetic models based on calcium and magnesium binding to a monochloro-monooxalato ring-opened anionic oxaliplatin intermediate fitted the in vitro degradation time-course data. In cancer patients, calcium and magnesium plasma concentrations varied and were increased by giving calcium gluconate and magnesium sulfate infusions, but did not alter or correlate with oxaliplatin clearance. The intrinsic in vitro clearance of oxaliplatin attributed to chloride-, calcium- and magnesium-mediated degradation predicted contributions of <2.5% to the total in vivo clearance of oxaliplatin. In conclusion, calcium and magnesium accelerate the in vitro degradation of oxaliplatin by binding to a monochloro-monooxalato ring-opened anionic intermediate. Kinetic analysis of in vitro oxaliplatin stability data can be used for in vitro prediction of potential effects on oxaliplatin clearance in vivo.
format	article
author	Catherine H. Han Prashannata Khwaounjoo Andrew G. Hill Gordon M. Miskelly Mark J. McKeage
author_facet	Catherine H. Han Prashannata Khwaounjoo Andrew G. Hill Gordon M. Miskelly Mark J. McKeage
author_sort	Catherine H. Han
title	Predicting effects on oxaliplatin clearance: in vitro, kinetic and clinical studies of calcium- and magnesium-mediated oxaliplatin degradation
title_short	Predicting effects on oxaliplatin clearance: in vitro, kinetic and clinical studies of calcium- and magnesium-mediated oxaliplatin degradation
title_full	Predicting effects on oxaliplatin clearance: in vitro, kinetic and clinical studies of calcium- and magnesium-mediated oxaliplatin degradation
title_fullStr	Predicting effects on oxaliplatin clearance: in vitro, kinetic and clinical studies of calcium- and magnesium-mediated oxaliplatin degradation
title_full_unstemmed	Predicting effects on oxaliplatin clearance: in vitro, kinetic and clinical studies of calcium- and magnesium-mediated oxaliplatin degradation
title_sort	predicting effects on oxaliplatin clearance: in vitro, kinetic and clinical studies of calcium- and magnesium-mediated oxaliplatin degradation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/4d56bc64c892498384d45ce82fe2a83d
work_keys_str_mv	AT catherinehhan predictingeffectsonoxaliplatinclearanceinvitrokineticandclinicalstudiesofcalciumandmagnesiummediatedoxaliplatindegradation AT prashannatakhwaounjoo predictingeffectsonoxaliplatinclearanceinvitrokineticandclinicalstudiesofcalciumandmagnesiummediatedoxaliplatindegradation AT andrewghill predictingeffectsonoxaliplatinclearanceinvitrokineticandclinicalstudiesofcalciumandmagnesiummediatedoxaliplatindegradation AT gordonmmiskelly predictingeffectsonoxaliplatinclearanceinvitrokineticandclinicalstudiesofcalciumandmagnesiummediatedoxaliplatindegradation AT markjmckeage predictingeffectsonoxaliplatinclearanceinvitrokineticandclinicalstudiesofcalciumandmagnesiummediatedoxaliplatindegradation
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Predicting effects on oxaliplatin clearance: in vitro, kinetic and clinical studies of calcium- and magnesium-mediated oxaliplatin degradation

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